Engineering epidermal growth factor for enhanced mitogenic potency.

C C Reddy; S K Niyogi; A Wells; H S Wiley; D A Lauffenburger

doi:10.1038/nbt1296-1696

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PubMed · 9634854

Engineering epidermal growth factor for enhanced mitogenic potency.

C C Reddy·S K Niyogi·A Wells·H S Wiley·D A Lauffenburger

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Abstract

Successful use of growth factors in therapeutic and bioprocessing applications requires overcoming two attenuation mechanisms: growth factor depletion and receptor down-regulation. Current ameliorative strategies use physiologically inappropriate high growth-factor concentrations, along with periodic media refeeding in vitro and reinjection or controlled-release devices in vivo. We demonstrate a new approach derived from understanding how these attenuation mechanisms arise from ligand/receptor trafficking processes. Specifically, a recombinant epidermal growth factor (EGF) mutant with reduced receptor binding affinity is a more potent mitogenic stimulus for fibroblasts than natural EGF or transforming growth factor alpha because of its altered trafficking properties.

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3T3 Cells Animals Cell Division Down-Regulation Epidermal Growth Factor ErbB Receptors Fibroblasts Gene Expression Regulation Genetic Engineering Mice Mitogens Mutation Recombinant Proteins Signal Transduction Transforming Growth Factor alpha Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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C C Reddy, S K Niyogi, A Wells, H S Wiley, D A Lauffenburger. 1996. Engineering epidermal growth factor for enhanced mitogenic potency.. https://doi.org/10.1038/nbt1296-1696

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